Combined LC/MS and GC/MS Approach for Analysis of Extractables and Leachables in Complex Matrices Using High Resolution Mass Spectrometry

Significance of the topic

Extractable and leachable analysis is crucial for ensuring the safety and performance of medical devices and polymeric materials. A combined high‐resolution GC/MS and LC/MS approach delivers comprehensive chemical coverage of diverse compound classes.

Study objectives and overview

The study aimed to establish and validate a non‐targeted workflow integrating GC/Q‐TOF and LC/Q‐TOF mass spectrometry. Rubber syringe gaskets and four catheter types were selected to evaluate extractables over extended extraction periods.

Methodology and instrumentation

• Sample preparation: Rubber gaskets extracted in tetrahydrofuran at ambient temperature for six months; catheters in ethanol:water (1:1) at 37 °C for three weeks.
• GC/Q‐TOF: Agilent 8890 GC with 7250 Q‐TOF, DB‐5Q column, splitless injection, oven program 45–325 °C, mass range 50–1000 m/z.
• LC/Q‐TOF: Agilent 1290 Infinity II LC with Revident LC/Q‐TOF, PS AQ‐C18 column, gradient water/methanol with 2.5 mM ammonium formate and 0.05 % formic acid, positive ESI, data‐dependent MS/MS (40–1700 m/z).
• Data analysis: MassHunter Unknowns Analysis with molecular feature extraction, Personal Compound Database Library, ExactMass tool for formula confirmation, and Mass Profiler Professional for statistical evaluation.

Main results and discussion

• GC/MS uniquely detected nonpolar hydrocarbons, phthalates, antioxidants and amide derivatives; LC/MS captured polar oxygenates, acids and oligomeric species.
• The new DB‐5Q column exhibited significantly reduced bleed at 325 °C, improving sensitivity and confidence in identifications.
• PCA clustering, volcano plots and Venn diagrams revealed distinct and overlapping extractable profiles among catheter types, reflecting material‐specific leachables.

Benefits and practical applications

• A dual‐technique workflow provides broad, complementary detection of extractables and leachables, supporting regulatory testing.
• High‐resolution accurate mass spectrometry and advanced data processing ensure reliable non‐targeted screening.
• Centralized data management and integrity via OpenLab ECM XT facilitate QA/QC compliance and traceability.

Future trends and potential applications

• Standardization of extraction protocols and unified multi‐platform workflows for diverse polymeric materials.
• Integration of machine learning and AI for accelerated feature annotation and risk assessment.
• Adoption of novel stationary phases and ionization methods to expand chemical space coverage.
• Application of non‐targeted workflows to pharmaceutical packaging, food contact materials and regulatory toxicology.

Conclusion

A combined GC/Q‐TOF and LC/Q‐TOF method enables comprehensive, high‐confidence non‐targeted analysis of extractables and leachables in complex polymer matrices, supporting material characterization, safety assessment and regulatory compliance.